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J J van Wyk

Publications and source records attributed to J J van Wyk.

12 recordsLinked to original sources
PubMed1989

Insulin-like growth factor stimulation of chondrocyte proteoglycan synthesis by human synovial fluid.

We investigated the role of insulin-like growth factors (IGFs) as regulating factors of cartilage metabolism in human synovial fluid (SF), using a bovine explant culture system that was shown to respond to recombinant IGF-1 in vitro. SF from rheumatoid arthritis (RA) patients and from control patients was found to stimulate chondrocyte proteoglycan synthesis in bovine articular cartilage. A monoclonal antibody directed primarily against IGF-1 (and to some extent, IGF-2) partially blocked the stimulatory action of serum and totally blocked the stimulation by SF. These findings indicate that IGFs are major regulating factors of cartilage proteoglycan synthesis in human SF. In addition, we measured serum and SF levels of IGF-1 in RA patients and control patients, using a radioimmunoassay. No difference in immunoreactive serum IGF-1 was detected between patients and controls. The IGF-1 levels in SF were consistently lower than in serum, for both patient groups. No differences in IGF-1 concentration were found between RA and non-RA SF. The relevance of these data with respect to joint inflammation is discussed.

Arthritis, Rheumatoid↗
PubMed1987

Isolation of rat testis cDNAs encoding an insulin-like growth factor I precursor.

We have characterized rat testis cDNAs encoding insulin-like growth factor I (IGF-I) precursor to facilitate studies of IGF-I expression in the male reproductive system. Two clones, P2 and P3, with inserts of 786 and 1200 bp, respectively, were isolated from a lambda gt11 library of rat testis cDNAs. The longest open reading frame of cDNA P2 predicts a 153-amino-acid residue IGF-I precursor that has only 11 amino acid substitutions compared with a human IGF-IA precursor encoded by a human liver mRNA. Three substitutions are within the predicted rat IGF-I sequence: a Pro for Asp in the B domain, an Ile for Ser in the C domain, and Thr for Ala in the D domain. Only two substitutions distinguish the predicted rat sequence from a mouse liver IGF-IA precursor: Thr for Ala in the signal peptide and Ala for Ser in the D domain. P2 hybridizes with poly(A)+ mRNAs of 7.5, 4.7, 1.7, and 1.2-0.9 kb in rat liver and testis. The other testis cDNA, P3, appears to represent a partially processed rat IGF-I mRNA precursor. By comparing the sequence of cDNA P2 with that of cDNA P3 and a 2.3-kb rat IGF-I genomic fragment, we predict exon splice sites within the codon for residue 26 and between residues 86-87 of the rat IGF-I precursor. Both of the predicted splice sites align with exon-intron junctions in the human IGF-I gene. We conclude, therefore, that IGF-I is synthesized as a precursor in the rat testis and that the structure of IGF-I genes, mRNAs, and precursors are highly conserved across species.

Animals↗
PubMed1986

Independent and synergistic actions of somatomedin-C in the stimulation of proteoglycan biosynthesis by cultured rat granulosa cells.

The role of somatomedin-C (Sm-C) in the regulation of granulosa cell proteoglycan biosynthesis was investigated in vitro in a primary culture of rat granulosa cells labeled with [35S]sulfate. Basal [35S]sulfate incorporation into extracellular proteoglycans was increased by 93 percent in response to treatment with highly purified Sm-C (50 ng/ml) by itself. Whereas treatment with a minimally effective dose of FSH (20 ng/ml) alone produced a 43 percent increase over basal levels in extracellular [35S]sulfate-labeled proteoglycans, concurrent treatment with Sm-C yielded a 2.7-fold amplification of the FSH effect. Qualitatively similar results were obtained when [35S]sulfate incorporation into cellular proteoglycans was determined, the latter accounting for approximately one half of the total radioactivity incorporated. Significantly, fractionation of the major extracellular proteoglycan species revealed FSH to favor the exclusive production of dermatan sulfate (1.6-fold increase), whereas Sm-C supported the simultaneous biosynthesis of both heparan and dermatan sulfate (2.5- and 1.8-fold increments, respectively). Moreover, Sm-C proved capable of diverting FSH-driven proteoglycan biosynthesis from the exclusive stimulation of dermatan sulfate towards the enhanced production of heparan sulfate over dermatan sulfate. These findings suggest that while Sm-C may synergize with FSH in stimulating granulosa cell proteoglycan biosynthesis, it is also able to act in tis own right to effect marked quantitative as well as qualitative alterations in proteoglycan economy. Given the possible role of proteoglycans in follicular antrum formation and follicular atresia, our findings raise the possibility that Sm-C of granulosa cell origin may partake in the growth as well as the demise of the developing ovarian follicle.

Animals↗
PubMed1984

Stimulation by somatomedin-C of aminoisobutyric acid uptake in human fibroblasts: a possible test for cellular responsiveness to somatomedin.

The effect of purified somatomedin-C (Sm-C)/insulin-like growth factor I on the uptake of alpha-aminoisobutyric acid (AIB) by confluent cultures of human fibroblasts was studied. An increase in [3H]AIB uptake was observed within 30 min of Sm-C addition, and a maximal effect was reached at 2.5 h (averaging 200% of control AIB uptake). Under the conditions employed, less Sm-C was required for maximal stimulation of [3H]AIB uptake (10 ng/ml in most cell lines) than for a maximal effect on [3H]thymidine incorporation (greater than 30 ng/ml). In multiple experiments with different lines of foreskin-derived and nongenital fibroblasts, the concentration of Sm-C resulting in half-maximal stimulation of [3H]AIB uptake was reproducible and was between 1.7 and 4.8 ng/ml in all cell lines tested except one. No significant difference was observed in the Sm responsiveness of cells from newborns and that of those from normal older children. Determination of binding of [125I]Sm-C to confluent monolayers of one fibroblast line revealed that the concentration of Sm-C resulting in half-maximal binding was nearly identical to that producing half-maximal [3H]AIB uptake stimulation. Stimulation of AIB uptake by an optimal concentration of epidermal growth factor (5 ng/ml) was also determined in several normal cell lines and was consistently close to 140% of the control value. Since epidermal growth factor and Sm interact with different receptors, this response may be a useful measure of cell integrity which is independent of the Sm receptor. The techniques for measurement of AIB uptake described in this report may prove useful in determining whether some children with growth failure of unknown etiology have target cell resistance to Sms.

Adolescent↗